Transdermal therapeutic system comprising buprenorphine

Abstract

The invention is concerned with a transdermal therapeutic system (TTS) comprising buprenorphine and a method of manufacturing such a TTS. The transdermal therapeutic system is used for the transdermal administration of buprenorphine and analogues thereof. In particular, the invention relates to the use of a transdermal therapeutic system (TTS) for analgesic purposes. The TTS according to the invention comprises a transdermal drug delivery composition comprising buprenorphine and an adhesive component, which is a mixture of a crosslinked and a non-crosslinked acrylic polymer and a penetration enhancer comprising a keto acid.

The invention claimed is: 
     
       1. A transdermal therapeutic system comprising:
 1) a backing layer, 
 2) at least one drug containing adhesive layer containing a transdermal drug delivery composition consisting of:
 i. 5 to 15% by weight of buprenorphine, based on the total weight of the composition, 
 ii. an adhesive component, which preferably forms an amorphous mass, comprising 20 to 50% by weight of a crosslinked acrylic polymer and 5 to 25% by weight of a non-crosslinked acrylic polymer, based on the total weight of the composition, in a ratio of 80 to 20 parts by weight to 60 to 40 parts by weight, 
 iii. and 5 to 15% by weight of levulinic acid, based on the total weight of the composition, 
 iv. 10 to 20% by weight of oleyl oleate, based on the total weight of the composition, and 
 v. 5 to 15% by weight of polyvinyl pyrrolidone, based on the total weight of the composition; and 
 
 3) optionally at least one further adhesive layer, and 
 4) further optionally, a release liner, 
 wherein the crosslinked acrylic polymer is obtained from one or more non-functional monomers and one or more functional monomers, the functional monomer comprising a carboxy group, an epoxy group and/or a hydroxy group, 
 wherein the transdermal therapeutic system releases buprenorphine in an amount sufficient to achieve a constant blood plasma of at least 200 pg/ml for up to 4 days. 
 
     
     
       2. The transdermal therapeutic system according to  claim 1 , wherein the functional monomer is selected from the group consisting of acrylic acid, methacrylic acid, (meth)acrylic acid hydroxy alkylester, 2-hydro-xylethyl acrylate and glycidyl methacrylate. 
     
     
       3. The transdermal therapeutic system according to  claim 1 , wherein the non-crosslinked acrylic polymer is obtained from monomers comprising one or more (meth)acrylic acid alkyl esters, optionally one or more of a n-alkyl acrylamide, and further optionally one or more of a vinyl ester, or mixtures thereof. 
     
     
       4. The transdermal therapeutic system according to  claim 3 , wherein:
 the (meth)acrylic acid alkyl ester is selected from the group consisting of 2-ethylhexyl acrylate, butyl acrylate, methyl acrylate and methyl methacrylate, 
 the monomers further comprise an n-alkylacrylamide comprising t-octyl acrylamide, and 
 the monomers further comprise a vinyl ester comprising vinyl acrylate. 
 
     
     
       5. The transdermal therapeutic system according to  claim 1 , wherein the crosslinked acrylic polymer and the non-crosslinked acrylic polymer are present in a ratio of crosslinked : non-crosslinked of 78:22 to 65:35 parts by weight. 
     
     
       6. The transdermal therapeutic system according to  claim 1 , wherein the crosslinked acrylic polymer and the non-crosslinked acrylic polymer are present in a ratio of crosslinked : non-crosslinked of 76:24 to 67:33 parts by weight. 
     
     
       7. The transdermal therapeutic system according to  claim 1 , wherein the crosslinked acrylic polymer and the non-crosslinked acrylic polymer are present in a ratio of crosslinked : non-crosslinked of about 70:30 parts by weight.